Serum and plasma separator {13 {0 constrictionless type

ABSTRACT

A self-contained fluid separator assembly capable of separating blood into its component parts of plasma or serum, the light phase, and cellular portion, the heavy phase, is disclosed. The assembly comprises a container having a first open end for receiving blood for subsequent separation, a second open end for removing separated plasma or serum and closures sealing the open ends of the container, the closures being formed of a self sealing elastomeric material which is penetrable by a cannula. A piston is slidably disposed in the container having its lateral outer surfaces in sealing contact with the inner surface of the container. Pressure responsive valve means is provided on the piston which is normally closed when there is a minimum pressure differential on each side of the piston and the valve means automatically opens in response to a substantial pressure differential so that when the container is subjected to centrifugal force the blood separates into its light phase and heavy phase and the valve means automatically opens with the light phase passing through the valve means so that the piston moves down through the light phase while retaining sealing engagement with the inner surface of the container. Filter means is mounted on the piston so as to filter the light phase prior to its reaching the valve means. When the piston descends to the interface the heavy phase cellular material clogs the filter, thereby preventing flow of fluids and solids to the valve. The incompressible heavy phase beneath the piston stops further piston descent, the pressure differential is terminated and the valve means automatically shifts from the open position to the closed position to provide an impervious barrier between the separated phases of the blood.

United States Patent 1 1 Ayres 1 1 June 24, 1975 1 SERUM AND PLASMA SEPARATOR CONSTRICTIONLESS TYPE Waldemar A. Ayres, Rutherford, NJ.

[73] Assignee: Becton, Dickinson and Company,

East Rutherford, NJ,-

221 Filed: Feb. 27, 1974 1211 Appl. No.: 446,363

[75] Inventor:

[52] U.S. Cl. 210/136; 210/314, 210/359; 210/516; 210/D1G. 23 151] int. Cl Bold 21/26 [58] Field of Search 23/230 B, 258.5, 259, 292; 128/2 F, 214 R, 218 M, 272; 210/83, 84,

131, 359, 5l4518, DIG. 23, D16. 24, 136,

Primary Examiner-Frank A. Spear, .lr.

Assistant Examiner-Robert G. Mukai Atlorney, Agent, or Firm-l(ane, Dalsimer, Kane, Sullivan and Kurucz [57] ABSTRACT A selfcontained fluid separator assembly capable of separating blood into its component parts of plasma or serum, the light phase, and cellular portion, the heavy phase, is disclosed. The assembly comprises a container having a first open end for receiving blood for subsequent separation, a second open end for removing separated plasma or serum and closures sealing the open ends of the container; the closures being formed of a self sealing elastomeric material which is penetrable by a cannula. A piston is slidably disposed in the container having its lateral outer surfaces in sealing contact with the inner surface of the container. Pressure responsive valve means is provided on the piston which is normally closed when there is a minimum pressure differential on each side of the piston and the valve means automatically opens in response to a substantial pressure differential so that when the container is subjected to centrifugal force the blood separates into its light phase and heavy phase and the valve means automatically opens with the light phase passing through the valve means so that the piston moves down through the light phase while retaining sealing engagement with the inner surface of the container. Filter means is mounted on the piston so as to filter the light phase prior to its reaching the valve means. When the piston descends to the interface the heavy phase cellular material clogs the filter, thereby preventing flow of fluids and solids to the valve. The incompressible heavy phase beneath the piston stops further piston descent, the pressure differential is terminated and the valve means automatically shifts from the open position to the closed position to provide an impervious barrier between the separated phases of the blood.

3 Claims, 2 Drawing Figures SERUM AND PLASMA SEPARA'IOR i CONSTRICTIONLESS TYPE BACKGROUND OF THE "INVENTION 1. Field of the Invention 1 i a The invention concerns apparatus for the separation and isolation of'blood plasma and blood serum from blood mixtures. 5

2. Brief Description of the Prior" Art It is known to separate blood into its component parts by centrifugation, particularly employing a sealed container such as is disclosed in US. Pat. No. 2,460.64]. This patent discloses a container having a closure at its open end which is capable'of being pene-' trated by a cannulathrotigh whichbloodipasses into the container. Clinical laboratories have heretofore used this device to collect'a blood-sample for subsequent separation into a light phas e, i'.e. the serum or plasma and the heavy p'ha-se; i.e. the cellular portion. The light phase isthen deeanted'fr'om the celltilar portion by any conventional means, *for example by the use =of a syringe fitted with a cannula,or'a' pipette, or the like.

An apparatus. also heretofore employedfor the separation of blood isdis'closed inUzS. Pat. N0. 3,5 08,653. This patent discloses a self-contained assembly forseparation of body fluidsuch as blood irf which a'deformable piston is disposed in the container'and is positioned initially adjacent the stopper for closing thecontainer. After the blood to be separatedis'in the container the assembly is centrifuged. After the blood is separated, increased centrifugal force'is applied to the container, the seal between the inner surface-of the container and piston isbroltdn and thepiston is deformed, moving down-through the light phaseiwi th the light phase passing solely around the" lateral surfaces of I the piston and the inner surfaces of the. container.

When the piston reaches the interface, between the light phase and the heavy phase, the pistonimovement is stopped, the force 'is terminated. and the sealis reestablished between the'inner surface of the container and the resilient piston to present a" bam'erjbetween the two phases. a w Disclosed in my US. Pat No. 3,779,383 is a serumplasma separator wherein the piston component is disclosed as having a valve means in'association therewith through which the light phase bloodicomponent passes during piston descent by centrifug ation In recognition of the fact that small particles ofsolid materials normally found in blood may be carried with liquid compo,- nents through the valve means; a preferred enibodiment of the apparatussdisclosed' inmy US. Pat. No. 3.779.383 has a filtei' disposed in-the passage leading to the valve means, however the filter element of my prior invention is ncit disclosed as a type which'willalso serve to stop the descent of t'he piston at the interface between the two bloodphases'. Y

By the present invention the requirement for a filter element is such that only light phase blood components pass through the iialve nieans. The-filter'means also comprises a means of stopping the piston descerit atthe most desirable point, he at the interfacebetween the separated blood phases. t Other devices known to the art are generally the filtration devices which separate blood into its component' phases such as'thos'e disclosed'iri UtSR Pat. Nos.

3,481,477 and 35121940.

SUMMARY OF THE INVENTION The invention is a self-contained fluid separator assembly capable of separating blood into its component parts of plasma or serum and cellular portion, comprising:

a. a container having a first open end which is adapted to receive blood for subsequent separation into a light phase and a heavy phase and a second open end for removing the separated light phase;

b. closures sealing the open ends of the container, the

closures being formed of a self-sealing elastomeric material which is penetrable by a cannula;

c. a piston having a specific gravity greater than the cellular. portion of the blood and slidably mounted in the container and having means on an outer surface in sealing engagement with an inner surface of the container; 1

d. pressure responsive valve'means associated with said piston, said valve means being normally closed when. thereis a minimum of pressure differential on different portions of the valve, means and which automatically opens in response to a substantial pressure differentialso that when said container is subjected to moderate centrifugal force the blood separates into its light phase and heavy phase but the piston stays in the upper portion of the container,- and subsequently ,when increased centrifugal force is used the valve means auto matically opens with the light phase passing up through the valve means enabling the piston to move down through the light phase while retaining sealing engagement with the inner surfaces of the container; and

e. filter and stop means associated with said piston which comprises a first filter member which will pass red blood corpuscles therethrough but will not pass fibrin and fibrous constituents of blood and a second filter member which will pass the light phase of blood but which will not pass red blood corpuscles therethrough.

BRIEF DESCRIPTION or THE DRAWINGS DETAILD DESCRIPTION OF THE INVENTION For a better understanding of the invention, a description of the drawings of the illustrative embodiments is had particularly with respect to the embodiments shown in FIGS. 1 and 2.

Referring to FIG. I, it is seen that the separator assembly 10 comprises a tubular member or container 12 having mounted in each open end ll, 15 closures l4 and 16. Closures l4 and 16 are made of a self-sealing elastomeric material, such as rubber, which are capable of receiving cannula l8 penetrated therethrough as illustrated in FIG. 1, for conducting blood 5 into the container. When the cannula is removed the closure is resealed with no loss of blood 5 passing through the penetration portion as illustrated in FIG. 2.

Closure 14 is formed having a depending cylindrical body portion 20 and a flanged head portion 22 integrally formed therewith. Body portion 20 has a diameter slightly greater than the internal diameter of the container 12 so that closure 14 when mounted into end ll provides a pressure fit to seal the end. Head portion 30 of stopper 16 is preferably shaped in the form of a hexagon and is slightly greater in diameter than body portion 28 which permits the assembly to be positioned on its side without danger of rolling. An axial recess 24 in stopper 14 is provided for easy access through the stopper, which reduces the force required to penetrate it with cannula 18.

Stopper 16 is formed preferably of the same material as stopper 14. Stopper 16 has a cylindrical body portion 28 and an integrally formed flange head portion 30.

As shown in FIG. 1, piston 40 is held in a position adjacent to stopper 16 by an interference fit between the inner surface 13 of container 12 and a plurality of axially spaced sealing rings 50. This is the normal position of piston 40 prior to separation of the blood mixture 5.

Piston 40 includes a tubular metal insert 52 which is mounted in annular recess 54 of piston 40. Metal insert 52 is preferably made of stainless steel or other rigid, chemically inert material having a specific gravity greater than blood. Piston 40 is formed of elastomeric material and is provided with annular recess 54 which is dimensioned to receive tubular member 52 in an interference fit so that no air space remains in annular recess 54.

The elastomeric portion of piston 40 comprises an outer wall 48 and spaced therefrom is inner wall 46 which defines annular recess 54. Formed integrally with wall 48 are a plurality of axially spaced sealing rings 50 which contact the inner wall surface 13 of container 12 in sealing engagement. Piston 40 when mounted in container 12 will maintain sealing contact with the inner surface 13 of container 12 throughout its path of travel within container 12, as hereinafter described. lntegral with and joining the lateral inner wall 46 is top wall portion of diaphragm 44 which is pierced by at least one aperture 42. During the centrifuging operation piston 40 is subjected to centrifugal forces tending to slide the piston downwardly and such descent establishes a pressure differential on opposite sides of the diaphragm 44 of piston 40. Top wall portion or diaphragm 44 has a relatively small thickness and lies adjacent stopper 16 in its initial position as seen in FIG. 1.

Diaphragm 44 is made of a resilient material. Wall portion 46 and diaphragm 44 of piston 40 define an axial annular recess or throat 80 within piston 40 which leads from the lower surface 82 of piston 40 to apertures 42. As the assembly is being subjected to centrifugal forces the light phase which is separated from the blood will pass into throat 80 and be guided to apertures 42 as the piston descends through the light phase. Since the centrifugal forces acting on the descending piston 40 will generate hydrostatic force greater than the force of the light phase being exerted against the top of the diaphragm 44, apertures 42 will automatically open and will enable piston 40 to move from its initial position of FIG. 1, downward within the confines of container 12. interposed in the flow path of light phase material to apertures 42 is a fine filter element 85 which has pore sizes which will not permit the passage of blood red cells, having an average diameter of about 7 microns. This element 85 serves as a stop means to halt the descent of piston 40 once it reaches the interface between the separated lighter and heavier phases as will be discussed more fully hereinafter. Affixed beneath filter 85 there is a different filter element 90 characterized by pore sizes which will allow the passage of red blood cells but will not allow the passage of particulate matter such as. for example fibrin. The filter element 90 as shown in FIG. 1 may have an interior chamber portion to provide increased filter surface area. This is a preferred form of filter element 90. However a filter element 90 completely filling the remaining void in throat may alternatively be employed.

In operation, the light phase passing through filter 90 on its way to apertures 42 is filtered to remove particles of fibrin and other particulate matter. When piston 40 reaches the heavy phase. red blood corpuscles contained therein pass intothroat 80, through filter 90 and are stopped from further passage by the red-blood cell impervious filter element 85, As the red blood cells build up on the surface of filter 85, they clog the filter and prevent the continued flow of fluid to apertures 42. The reduction of flow and the further incompressibility of the heavy phase halts further descent of piston 40. This occurs when the piston 40 has reached a point in its descent approximating the interface between light 5a and heavy 5b separated blood phases as seen in FIG. 2. When piston 40 stops its movement in container 12 and comes to rest at the aforementioned interface, the pressure differential on each side of diaphragm 44 is substantially equalized and valve means 42 automatically shifts from the open position to the closed position even though the assembly may continue to be subjected to centrifugal forces.

As illustrated in FIG. 2. piston 40 has completed its travel within container 12 and is stopped from further movement in container 12 by the clogging of filter 85, which acts as a stop means. With the valve aperture means 42 closed, the piston 40 forms an impermeable barrier between the now separated and isolated phases.

Fine filter element may be made of any conventional filter material capable of preventing the passage of red blood corpuscles (which have an average effective diameter of about 7 microns) but which will allow the passage of blood serum or blood plasma. The materials employed should not produce any undesirable reaction with blood. lllustrative of filter materials for filter which may be employed are asbestos, compacted fibers of polyolefins, plastic foams such as polyurethane foams, polyethylene foams and the like; sintered glass and sintered polyethylene.

When operating the separator assembly of the invention herein it is preferred that the assembly be first evacuated of air so that when cannula l8 penetrates closure 14 blood 5 will automatically fill container 12. After cannula I8 is withdrawn and container 12 is filled with blood the assembly may be placed in a centrifuge and is separated into light and heavy phases by employing relatively low centrifugal forces which do not cause the piston to move from its initial position. Thereafter the rotational speed of the centrifuge is increased which causes descent of piston 40 through the light phase. When the centrifugal forces are terminated, the separated and phase isolated blood samples are ready for use in a conventional manner for the diagnosis of physical ailments.

I claim:

1. A self-contained fluid separator assembly capable of separating blood into its component light phase of plasma or serum and heavy phase or cellular portion comprising:

a. a container having a first open end which is adapted to receive blood for subsequent separation into a light phase and a heavy phase and a second open end for removing the separated light phase;

b, closures sealing the open ends of the container, the closures being formed of a self sealing elastomeric material which is penetrable by a cannula;

c. a piston having a specific gravity relatively greater than the cellular portion of the blood and slidably mounted in the container and having means on an outer surface for providing sealing engagement with an inner surface of the container;

d. pressure responsive valve means associated with said piston, said valve means being constructed and arranged to be normally closed when there is a minimum of pressure differential on opposite sides of the valve means and which automatically opens in response to a substantial pressure differential so that when said container is subjected to moderate centrifugal force the blood separates into its light phase and heavy phase but the piston stays in the upper portion of the container, and subsequently when increased centrifugal force is used the valve means automatically opens with the light phase passing up through the valve means enabling the piston to move down through the light phase while retaining sealing engagement with the inner surfaces of the container; and

e. filter and stop means associated with said piston which comprises a first filter member which has a porosity selected such that it will pass red blood corpuscles and serum therethrough but will not pass fibrin and fibrous constituents of blood and a second filter member which has a porosity selected such that it will pass serum but will not pass red blood corpuscles therethrough; said first filter being mounted on said piston in a position wherein the light phase of the blood which is filtered passes therethrough before contacting said second filter member.

2. The self-contained fluid separator of claim 1 wherein said container comprises a tubular body open at each end in which closures formed of elastomeric material are mounted in sealing engagement with the tubular body and a piston disposed adjacent one of said closures.

3. The self-contained fluid separator of claim 1 wherein the piston includes a rigid tubular sleeve mounted in a generally tubular body portion formed of elastomeric material and having a plurality of spaced axial sealing rings on its outer portion for sealing engagement with the inner wall of the container and a diaphragm forming a wall across one end of the generally tubular elastomeric sleeve and wherein said valve means is comprised of at least one resilient aperture formed in said diaphragm. 

1. A SELF-CONTAINED FLUID SEPARATOR ASSEMBLY CAPABLE OF SEPARATING BLOOD INTO ITS COMPONENT LIGHT PHASE OF PLASMA OR SERUM AND HEAVY PHASE OR CELLULAR PORTION COMPRISING: A/ A CONTAINER HAVING A FIRST OPEN END WHICH IS ADAPTED TO RECEIVE BLOOD FOR SUBSEQUENT SEPARATION INTO A LIGHT PHASE AND A HEAVY PHASE AND A SECOND OPEN END FOR REMOVING THE SEPARATED LIGHT PHASE; B. CLOSURES SEALING THE OPEN ENDS OF THE CONTAINER, THE CLOSURES BEING FORMED OF A SELF SEALING ELASTOMERIC MATERIAL WHICH IS PENETRABLE BY A CANNULA; C. A PISTON HAVING A SPECIFIC GRAVITY RELATIVELY GREATER THAN THE CELLULAR PORTION OF THE BLOOD AND SLIDABLY MONUTED IN THE CONTAINER AND HAVING MEANS ON AN OUTER SURFACE FOR PROVIDING SEALING ENGAGEMENT WITH AN INNER SURFACE OF THE CONTAINER; D. PRESSURE RESPONSIVE VALVE MEANS ASSOCIATED WITH SAID PISTON, SAID VALVE MEANS BEING CONSTRUCTED AND ARRANGED TO BE NORMALLY CLOSED WHEN THERE IS A MINIMUM OF PRESSURE DIFFERENTIAL ON OPPOSITE SIDES OF THE VALVE MEANS AND WHICH AUTOMATICALLY OPENS IN RESPONSE TO A SUBSTANTIAL PRESSURE DIFFERENTIAL SO THAT WHEN SAID CONTAINER IS SUBJECTED TO MODERATE CENTRIFUGAL FORCE THE BLOOD SEPARATES INTO ITS LIGHT PHASE AND HEAVY PHASE BUT THE PISTON STAYS IN THE UPPR PORTION OF THE TONTAINER, AND SUBSEQUENTLY WHEN INCREASED CERTRIFUGAL FORCE IS USED THE VALVE MEANS AUTOMATICALLY OPENS WITH THE LIGHT PHASE PASSING UP THROUGH THE VALVE MEANS ENABLING THE PISTON TO MOVE DOWN THROUGH THE LIGHT PHASE WHILE RETAINING SEALING ENGAGEMENT WITH THE INNER SURFACES OF THE CONTAINER; AND E. FILTER AND STOP MEANS ASSOCIATED WITH SAID PISTON WHICH COMPRISES A FIRST FILTER MEMBER WHICH HAS A POROSITY SELECTED SUCH THAT IT WILL PASS RED BLOOD CORPUSCLES AND SERUM THERETHROUGH BUT WILL NOT PASS FIBRIN AND FIBROUS CONSTITUENTS OF BLOOD AND A SECOND FILTER MEMBER WHICH HAS A POROSITY SELECTED SUCH THAT IT WILL PASS SERUM BUT WILL NOT PASS RED BLOOD CORPUSCLES THERETHROUGH; SAID FIRST FILTER BEING MOUNTED ON SAID PISTON IN A POSITION WHEREIN THE LIGHT PHASE OF THE BLOOD WHICH IS FILTERED PASSES THERETHROUGH BEFORE CONTACTING SAID SECOND FILTER MEMBER.
 2. The self-contained fluid separator of claim 1 wherein said container comprises a tubular body open at each end in which closures formed of elastomeric material are mounted in sealing engagement with the tubular body and a piston disposed adjacent one of said closures.
 3. The self-contained fluid separator of claim 1 wherein the piston includes a rigid tubular sleeve mounted in a generally tubular body portion formed of elastomeric material and having a plurality of spaced axial sealing rings on its outer portion for sealing engagement with the inner wall of the container and a diaphragm forming a wall across one end of the generally tubular elastomeric sleeve and wherein said valve means is comprised of at least one resilient aperture formed in said diaphragm. 